Secondary Data Analysis of the Data from Comparison of AMD Treatments Trials

描述(申请人提供)：建议的项目将利用年龄相关黄斑变性(AMD)治疗试验比较(CATT)的综合数据集，CATT是一项由美国国家眼科研究所赞助的多中心非劣势临床试验，以 评估雷尼比珠单抗(Lucentis)和贝伐单抗(阿瓦斯丁)每月或PRN(PRN)治疗的疗效和安全性。这项建议的具体目标不包括贸发会议研究的主要目标，这些目标已经实现。相反，拟议的项目涉及对CATT数据集的额外二次分析，以满足以下重要的新目标：(1)描述治疗2年期间视力随时间的反应模式，并确定(1或3次注射后)视力的短期反应是否预测长期(2年)视力反应。(2)描述治疗2年期间OCT和荧光素血管造影所捕捉到的形态变化，并评价3个月的形态反应是否可以预测2年后的远期形态反应。(3)评价抗血管内皮生长因子治疗2年后视力与形态学改变的关系。(4)描述PRN患者治疗2年后的治疗模式，找出与治疗次数少有关的预后因素。(5)评估发病时新生血管性AMD的形态特征和严重程度与基因型和表型的关系。(6)探讨抗凝药物与新生血管性AMD患者视网膜出血的关系。CATT数据集是一种独特的资源，可以进一步评估Lucentis和阿瓦斯丁对视觉和形态变化的影响，阐明视觉和形态反应之间的关联，并确定可能与新生血管性AMD临床特征相关的因素(遗传和全身药物暴露)。CATT数据集的分析将为治疗眼科医生及其患者提供有用的信息，帮助监测和优化个性化药物对新生血管性AMD的治疗。非常大的样本量(N=1185)，高质量的数据集，以及调查人员的丰富经验和高生产率，以及CATT研究小组的全力支持，支持了高 建议项目的收益率。

DESCRIPTION (provided by applicant): The proposed project will utilize the comprehensive dataset from the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT), a multi-center non-inferiority clinical trial, sponsored by the National Eye Institute, to assess the efficacy and safety of ranibizumab (Lucentis) and bevacizumab (Avastin) when treated monthly or PRN (pro re nata). The specific aims of this proposal do not include the major goals of the CATT Study, which were already accomplished. Instead, the proposed project involves additional secondary analysis of the CATT dataset to address the following important new aims: (1) To describe the response pattern of visual acuity over time during the 2 years of treatment, and to determine whether the short-term response of visual acuity (after 1 or 3 injections) predicts the long-term (2 years) visual acuity response. (2) To describe the morphologic changes captured by OCT and fluorescein angiography over time during 2 years of treatment, and to evaluate whether the morphologic responses at 3 months predict the long-term morphologic responses at 2 years. (3) To assess the associations between vision and morphologic changes from anti- VEGF treatment at 2 years. (4) To describe treatment patterns and identify the prognostic factors associated with a low number of treatments in patients treated PRN for 2 years. (5) To assess genotype-phenotype associations with respect to the morphologic features and severity of neovascular AMD at presentation. (6) To evaluate the association of anticoagulation medications with retinal hemorrhage in patients with neovascular AMD. The CATT dataset is a unique resource to further evaluate the effects of Lucentis and Avastin on visual and morphologic changes, to elucidate the association between visual and morphologic responses, and to determine the factors (genetic and systemic drug exposure) that may be associated with features of neovascular AMD at presentation. The analyses of the CATT dataset will provide useful information to the treating ophthalmologists and their patients on what to expect from treatments, and to help monitor and optimize the treatment of the neovascular AMD by personalized medicine. The very large sample size (N=1185), high quality of the dataset, as well as the rich experience and high productivity of the investigators along with the full supports of the CATT Research Group, support the feasibility and likelihood of high yield of the proposed project.